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The degree to which mitochondrial-linked programmed cell death pathways contribute to skeletal muscle atrophy during cancer remains unknown. Here we combined a novel and robust mouse model of metastatic ovarian cancer with chronic administration of the mitochondrial-targeted antioxidant SkQ1 to determine the time-dependent and muscle-specific relationships of mitochondrial-linked apoptotic and necroptotic signalling to the development of muscle atrophy in the type IIB-rich gastrocnemius....

FGFR1 genetic alterations are associated with brain malignancies, including FGFR1 mutations in familial and sporadic cases of low-grade glioneuronal tumors, suggesting intrinsic mechanisms of selective pressure toward FGFR1 multiple events arising in the context of a quiet genome. To decipher the molecular mechanisms triggered by multiple concurrent FGFR1 mutations, we have mapped the proximal interactome of wild-type, single- and double-mutant FGFR1 proteins through a BioID-MS approach. Our...

CONCLUSIONS: Surprisingly, all cell types examined exhibited differences between patients and controls. Monocytes and NK cells, the cell types least likely to be directly impacted by thymic effects, had unique patterns of gene expression, although both were highly altered in patients. This suggests a widespread impact of the deletion that may be related to direct and indirect effects of reduced gene dosage.

To advance sustainable swine manure management through insect-mediated bioconversion, this study implemented a comparative evaluation of the flesh fly Boettcherisca peregrina (Robineau-Desvoidy) (Diptera: Sarcophagidae) and the blow fly Aldrichina grahami (Aldrich) (Diptera: Calliphoridae). We quantified: (i) larval viability and bioconversion efficiency under manure-fed conditions, (ii) nutritional profiles and heavy metal accumulation in larval biomass, and (iii) agronomic value and residual...

Variants in the familial hypercholesterolemia gene LDLR-the most important genetic driver of cardiovascular disease-can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and increase the risk of premature atherosclerosis. Definitive classifications are lacking for nearly half of clinically encountered LDLR missense variants, limiting interventions that reduce disease burden. Here, we tested the impact of ~17,000 (nearly all possible) LDLR missense coding variants on both...

CONCLUSION: Our results suggest that national rounds with centralized molecular review can direct AYA patients with CNS tumors toward targeted agents and clinical trials, while deferring radiation therapy. Taken together, our work details an ongoing effort to improve and standardize care of AYA patients with CNS tumors in Canada.

T-cell leukemias and lymphomas (TCLs) form a heterogeneous group of rare and often aggressive malignancies. Due to the rarity and heterogeneity of TCL subtypes, clinical trials are challenging to conduct, making pharmacogenomic studies in cell line panels critical for the discovery of targeted therapeutics. The scarcity of data repositories with integrated multi-omics and drug screening data hinders the preclinical evaluation of drug vulnerabilities and the identification of molecular markers...

CONCLUSIONS: Findings from this trial will provide critical insights into effective strategies for enhancing vaccine confidence and uptake in marginalized populations. By leveraging community-based approaches and local partnerships, this study aims to improve public health responses to vaccine-preventable diseases and contribute to global efforts to eradicate measles and polio. Furthermore, the findings will inform scalable interventions that can be adapted to similar contexts, potentially...

Oat grain is a traditional human food that is rich in dietary fibre and contributes to improved human health^(1,2). Interest in the crop has surged in recent years owing to its use as the basis for plant-based milk analogues³. Oat is an allohexaploid with a large, repeat-rich genome that was shaped by subgenome exchanges over evolutionary timescales⁴. In contrast to many other cereal species, genomic research in oat is still at an early stage, and surveys of structural genome diversity and gene...

CONCLUSIONS: We offer a gene-centric perspective to understand spatially coordinated expression between neighboring cells. Our method only requires the gene expression and cell location matrices to find cross-expressing gene pairs. The R package is available at https://github.com/gillislab/CrossExpression .

Cell migration is an enormously complex process that requires sophisticated regulation and exquisite coordination of many cellular proteins that must act in a temporally and spatially orchestrated manner to achieve directional motion. Much like neuromuscular control of gait and walking, except within a single cell, a series of rapid feedback mechanisms must act in a cyclical manner to result in movement. The protein-serine kinase Akt/PKB that acts downstream of phosphatidylinositol 3' kinase...

RNA-binding proteins (RBPs) are key mediators of post-transcriptional gene regulation, including splicing, transport, stability, and other facets of RNA metabolism. Many RBPs exert their function through sequence-specific protein-RNA interactions. RBP RNA-binding specificity models, or motifs, are thus essential for understanding post-transcriptional gene regulatory mechanisms. Here, we present CisBP-RNA (Catalog of inferred sequence Binding Preferences of RNA-binding proteins), a freely...

CONCLUSIONS AND RELEVANCE: Through a methodologically robust development process, the SOFA-2 score offers updated definitions to describe organ dysfunction in adult patients requiring critical care and readily quantifiable criteria to grade the degree of dysfunction in individual organ systems. This score considers contemporaneous changes in patient management and outcomes.

CONCLUSIONS AND RELEVANCE: The SOFA-2 score, updated to include contemporary organ support treatments and new score thresholds, describes organ dysfunction in a large, geographically and socioeconomically diverse population of critically ill adults.

CONCLUSION: Increased pain may be associated with myocardial ischemic events in the perioperative period in hip fracture patients. Future research is needed to confirm and further clarify this relationship, and to determine whether analgesic interventions can reduce the risk of perioperative myocardial ischemia.

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A key challenge in process optimization is reactor performance, particularly in light-dependent bioprocesses. While novel photobioreactor designs exist, adapting established bioreactors with simple media supplementation may provide a more practical and modular alternative to complex mechanical modifications. In this study, we evaluated the effect of supplementing 0.2 % (w/v) clay powder on acetate production by Rhodopseudomonas palustris grown on butyrate. Among the clay types tested, kaolin...

Fully automated self-driving laboratories promise high-throughput, large-scale scientific discovery by reducing repetitive labor. However, they require deep integration of laboratory knowledge, which is often unstructured, multimodal, and hard to incorporate into current AI systems. This paper introduces the "k-agents" framework, designed to support experimentalists in organizing laboratory knowledge and automating experiments with agents. The framework uses large-language-model-based agents to...

In solid tissues, homeostasis and post-injury regeneration involve a complex interplay among various cell types. The mammalian liver harbors numerous epithelial and non-epithelial cells, and the global signaling networks governing their interactions are unknown. To unravel the hepatic cell network, we purified 10 different cell populations from normal and regenerative mouse livers. Analyzing their transcriptomes unveiled ligand-receptor interactions and over 50,000 potential cell-cell...

Dependence on methamphetamine (METH) is a severe brain disorder characterized by high relapse rates and cognitive decline following detoxification. Recent research suggests that transcranial direct current stimulation (tDCS) may treat addiction, but the underlying neural mechanisms remain unknown. Here, we employed METH-conditioned place preference (CPP) paradigm integrated with fMRI, electrophysiology, chemogenetics, in vivo fiber photometry recordings and a novel rodent tDCS model to examine...